A calcium-stimulated serine protease from monkey brain degrades the β-amyloid precursor protein

Razzaboni, Bronwyn L.; Papastoitsis, Gregory; Koo, Edward H.; Abraham, Carmela R.

doi:10.1016/0006-8993(92)91279-n

Cited by 40 publications

(11 citation statements)

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“…Amounts of (-APP increase during neuronal differentiation (5-7) and in response to injury (8-10), suggesting possible physiologic roles for this molecule. Biological activities have been attributed to A(3 (11-13) and to secreted We sought to determine whether the mitogen-activated protein kinases (MAPKs) might be involved both in transducing the effects of (-APP and in regulating the phosphorylation state of T. MAPKs (also known as extracellular signal-regulated kinases or ERKs) are a family of protein kinases [40][41][42][43][44][45][46] kDa that specifically phosphorylate seine and threonine residues followed by proline (24). MAPKs are activated by a variety of trophic factors, often through stimulation of p21 (25)(26)(27) Abbreviations: P-APP, P-amyloid precursor protein; MAPK, mitogen-activated protein kinase; AD, Alzheimer disease; PHF, paired helical filament; CHO, Chinese hamster ovary; NGF, nerve growth factor; AP, amyloid P; ERK, extracellular signal-regulated kinase.…”

Section: Introductionmentioning

confidence: 99%

“…We sought to determine whether the mitogen-activated protein kinases (MAPKs) might be involved both in transducing the effects of (-APP and in regulating the phosphorylation state of T. MAPKs (also known as extracellular signal-regulated kinases or ERKs) are a family of protein kinases [40][41][42][43][44][45][46] kDa that specifically phosphorylate seine and threonine residues followed by proline (24). MAPKs are activated by a variety of trophic factors, often through stimulation of p21 (25)(26)(27).…”

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confidence: 99%

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Secreted beta-amyloid precursor protein stimulates mitogen-activated protein kinase and enhances tau phosphorylation.

Greenberg

Koo

Selkoe

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

150

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Biological effects related to cell growth, as well as a role in the pathogenesis of Alzhemer disease, have been ascribed to the -amyloid precursor protein (1-APP).Little is known, however, about the Intracellular cascades that mediate these effects. We report that the secreted form of 3-APP potently stimulates mitogen-activated protein kinases (MAPKs). (-APP), which appears in the medium of cultured cells and in cerebrospinal fluid (2-4). Amounts of (-APP increase during neuronal differentiation (5-7) and in response to injury (8-10), suggesting possible physiologic roles for this molecule. Biological activities have been attributed to A(3 (11-13) and to secreted We sought to determine whether the mitogen-activated protein kinases (MAPKs) might be involved both in transducing the effects of (-APP and in regulating the phosphorylation state of T. MAPKs (also known as extracellular signal-regulated kinases or ERKs) are a family of protein kinases [40][41][42][43][44][45][46] kDa that specifically phosphorylate seine and threonine residues followed by proline (24). MAPKs are activated by a variety of trophic factors, often through stimulation of p21 (25)(26)(27) Abbreviations: P-APP, P-amyloid precursor protein; MAPK, mitogen-activated protein kinase; AD, Alzheimer disease; PHF, paired helical filament; CHO, Chinese hamster ovary; NGF, nerve growth factor; AP, amyloid P; ERK, extracellular signal-regulated kinase.*To whom reprint requests should be addressed. 7104The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Secreted beta-amyloid precursor protein stimulates mitogen-activated protein kinase and enhances tau phosphorylation.

Greenberg

Koo

Selkoe

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

150

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“…A cathepsin G-like activity has been partially purified from the normal human and monke y brain and from the brain of Alzheimer subjects (Razzaboni et al, 1992); this proteolytic acti\ity appears to be sensitive to inhibition by the kallikrein inhibitor (aprotinin) and is localized in astrocytes, glial cells surrounding the neuritic plaque (Razzaboni et al .. 1992). Owing to this localization it has been hypothesized that this proteinase could be involved in processing the p-amyloid precursor and hence could influence formation and deposition of the p-amyloid.…”

Section: Discussionmentioning

confidence: 99%

Acid‐Stable Serine Proteinase Inhibitors in the Urine of Alzheimer Disease Subjects

et al. 1996

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A comparative study of the levels of acid-stable proteinase inhibitors (kallikrein and trypsin inhibitors) in the urine of healthy and Alzheimer subjects, of both sexes, has been performed. A preliminary characterization of the purified inhibitors indicates that the urinary antitryptic activity is accounted for by the presence of the well known Urinary Trypsin Inhibitor (UTI) while an apparently new molecule appears to be responsible for the anti kallikrein activity. The urinary levels of kallikrein inhibitors are very similar in healthy and sick subjects while the levels of trypsin inhibitors appear significatively increased in Alzheimer subjects of both sexes. The data presented here support the hypothesis that unpaired proteolytic processes could be involved in the pathogenesis of Alzheimer's disease and suggest that the levels of urinary acid-stable inhibitors may prove to be useful markers of the disease.

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“…The 'in vivo' significance of this finding can be accounted for by the potential role ascribed to chymotrypsin-like proteases in brain metabolism, with particular reference to the aetiology of AD and to the debated role of aluminum in the deregulation of the brain proteolytic processes, leading to the generation of senile plaques, which are the major hallmark of this neurological disorder [36,37]. In this context the aluminum role could be envisaged at different levels.…”

Section: Effects Of Aluminum On the Biological Activity Of Serine Promentioning

confidence: 99%

Aluminum modulation of proteolytic activities

Lupidi

Angeletti

Eleuteri

et al. 2002

Coordination Chemistry Reviews

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The effect of aluminum ions on the activity of proteolyic activities, mainly serine proteases and calpains, has been examined. Aluminum affects the biological activity of proteolytic activities either through a direct effect on the enzyme molecule or through a deregulation of the control mechanisms acting on them. Binding of the ion, most likely results in molecular rearrangements affecting both the substrates binding site and the site involved in the recognition of macromolecular inhibitors. As whole, the data reported clearly indicate that aluminum significatively affects the intracellular protein turnover, most likely triggering catastrophic events for the cellular life. The physiopathological significance of these effects has been discussed, in particular for neurological disorders (the Alzheimer's disease included) where an imbalance of proteolytic as well as antiproteolytic systems appears a crucial event both for the formation of neuritic plaques and neurofibrillary tangles which are the major hallmarks of the disease. #

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A calcium-stimulated serine protease from monkey brain degrades the β-amyloid precursor protein

Cited by 40 publications

References 37 publications

Secreted beta-amyloid precursor protein stimulates mitogen-activated protein kinase and enhances tau phosphorylation.

Secreted beta-amyloid precursor protein stimulates mitogen-activated protein kinase and enhances tau phosphorylation.

Acid‐Stable Serine Proteinase Inhibitors in the Urine of Alzheimer Disease Subjects

Aluminum modulation of proteolytic activities

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